Coronary arterial disease is one of the diseases deserving the utmost attention today. It is suspected that a variety of factors contribute in a complex way to arteriosclerosis which triggers coronary arterial disease but an increased blood level of cholesterol is a major factor and the more direct factor is the increase and oxidative degeneration of low-density lipoprotein (LDL) which comprises cholesterol particles.
For the prevention of arteriosclerosis, it is important to lower the blood cholesterol level. Statins reportedly produce marked cholesterol lowering effects in patients with hypercholesterolemia. Statins inhibit hydroxymethylglutaryl-CoA reductase, the rate-determining enzyme in cholesterol biosynthesis, to thereby interfere with cholesterol biosynthesis and through the consequent reduction in intrahepatic cholesterol content and ensuing increase in LDL receptors, lower the plasma cholesterol level. However, notwithstanding the fact that it is about a decade since this drub was developed, thee has been reportedly no change in the incidence of conronary arterial disease and it is, thus, insufficient to merely lower cholesterol alone for the inhibition of arteriosclerosis.
Regarding the etiologic mechanism of arteriosclerosis, the LDL oxide hypothesis is known. Thus, it is postulated that LDL is oxidized to ox-LDL, which is taken up in macrophages and the resulting foam cells are deposited on the arterial wall to cause progression of arteriosclerosis. Recent years have seen many research results endorsing this hypothesis. The antiarteriosclerotic effect of the antihyperlipidemic drug probucol is considered to arise from its antioxidant activity, not from its cholesterol-lowering activity. Thus, for the inhibition of arteriosclerosis, not only depression of the cholesterol level but also inhibition of the oxidation of LDL can be an effective means.
As a natural antioxidant occurring in LDL, coenzyme Q10 and vitamin E are known. Heretofore, in view of its abundant occurrence in LDL, vitamin E was once considered to be a central substance of antioxidant activity but recent studies have revealed that coenzyme Q10 is a more important factor. While coenzyme Q10 is a molecule synthesized in vivo, it is well known that its biosynthetic pathway involves hydroxymethylglutaryl-CoA as does the biosynthetic pathway of cholesterol and, therefore, the biosynthesis of coenzyme Q10 is also inhibited by said statins. Actually many cases have been reported in which the administration of a statin caused depressions in the plasma coenzyme Q10 level. Moreover, the administration of a statin reportedly rendered LDL more susceptible to oxidation and, therefore, the influence of a statin on coenzyme Q10 and, hence, on the oxidizability of LDL has been suspected. To deal with the above decrease in coenzyme Q10 caused by the administration of statin, attempts have been made to compensate for the decrease by administering coenzyme Q10 (JP-A 02-233611, U.S. Pat. No. 5,082,650, U.S. Pat. No. 5,316,765).
Coenzyme Q10 occurs in two forms, the oxidized form and the reduced form, and it is known that, in the living body, usually about 40 to 90% of the coenzyme exists in the reduced form. It is the reduced coenzyme Q10 that exhibits antioxidant activity within LDL particles and regardless of how large its amount is, the oxidized coenzyme Q10 does not expresses antioxidant activity at all. Therefore, for the inhibition of arteriosclerosis, it is necessary to increase the reduced coenzyme Q10 in the plasma. However, in the above-mentioned administration of coenzyme Q10, the oxidized coenzyme Q10 (ubiquinone) is invariably used.